Noradrenergic uptake in the liver on 123 I-mIBG imaging: Influence of heart failure and diabetes.

BACKGROUND AND AIM: Imaging noradrenergic uptake in the liver with norepinephrine analog 123 I-meta-iodobenzylguanidine (mIBG) was explored in normal controls and patients with heart failure (HF). METHODS: A total of 961 HF (343 with diabetes mellitus [DM]) and 94 control subjects underwent anterior planar mIBG images including upper abdomen at 15 min (early) and 3 h 50 min (late) post-injection. Decay-corrected liver activity normalized to injected activity and body surface area (counts/pixel [cpp]/MBq/m2 ) was compared in three groups: HF with DM; HF without DM; and controls. Associations with plasma norepinephrine, liver function tests, and level of cardiac innervation were explored. RESULTS: In controls, liver mIBG activity decreased over time (early: 2.78 vs late: 2.43 cpp/MBq/m2 , P < 0.0001); in HF subjects, activity increased during this interval (HF without DM: 2.85 vs 2.93 [P = 0.005]; HF with DM: 2.37 vs 2.43 [P = 0.054]). Early liver activity was lower in HF with DM subjects than in the other groups (P < 0.001); late liver activity was higher in HF without DM than in the other two groups (P < 0.01). Subjects with elevated plasma norepinephrine (> 520 pg/mL) or ≥ 1 abnormal liver function test had lower early and late liver activity. In subjects with preserved cardiac mIBG uptake, HF subjects had higher and control subjects lower liver activity than comparable subjects with decreased cardiac innervation. CONCLUSIONS: In HF subjects, liver mIBG activity increased over time, reversing the normal washout pattern, suggesting a compensatory change in sympathetic nerve function. DM, abnormal liver function tests, and decreased cardiac innervation were associated with decreased liver mIBG uptake in HF.

Assessment of 123I-mIBG and 99mTc-tetrofosmin single-photon emission computed tomographic images for the prediction of arrhythmic events in patients with ischemic heart failure: Intermediate severity innervation defects are associated with higher arrhythmic risk.

RATIONALE: 123I-mIBG planar image heart-to-mediastinum ratios effectively risk-stratify heart failure (HF) patients. The value of single-photon emission computed tomographic (SPECT) imaging for identifying increased risk of ventricular arrhythmias is less clear. This study sought to determine if findings from simultaneous interpretation of 123I-mIBG and 99mTc-tetrofosmin SPECT are predictive of arrhythmic events (ArEs). METHODS: 123I-mIBG SPECT images from 622 patients with ischemic HF were presented in standard displays alongside 99mTc-tetrofosmin images. Consensus interpretations using a 17-segment model produced summed scores. Cox proportional hazards analyses related findings to adjudicated ArEs over 2 years. RESULTS: 471 patients had images adequate for total 17-segment scoring. There were 48 ArEs (10.2%). Neither 123I-mIBG nor 99mTc-tetrofosmin SPECT summed scores were univariate predictors. On multivariate proportional hazards analysis, the 123I-mIBG SPECT score was independently predictive of ArEs (HR: 0.975, 95% CI 0.951-0.999, P = 0.042), but HR<1 indicated that risk decreased with increasing score. This occurred because patients with intermediately abnormal SPECT studies had a higher likelihood of ArEs compared to patients with extensive abnormalities. CONCLUSIONS: The presumption of a monotonic increase in ArE risk with increasing summed 123I-mIBG SPECT score may not be correct as ischemic HF patients with abnormalities of intermediate extent appear at highest risk.

Quantitative iodine-123-metaiodobenzylguanidine (MIBG) SPECT imaging in heart failure with left ventricular systolic dysfunction: Development and validation of automated procedures in conjunction with technetium-99m tetrofosmin myocardial perfusion SPECT.

BACKGROUND: The purpose of this study was to develop and validate new approaches to quantitative MIBG myocardial SPECT imaging in heart failure (HF) subjects. METHODS AND RESULTS: Quantitative MIBG myocardial SPECT analysis methods, alone and in conjunction with 99mTc-tetrofosmin perfusion SPECT, were adapted from previously validated techniques for the analysis of SPECT and PET perfusion imaging. To account for underestimation of MIBG defect severity in subjects with global reduction in uptake, a mixed reference database based on planar heart/mediastinum (H/M) ratio categories was used. Extent and severity of voxel-based defects and number of myocardial segments with significant dysinnervation (derived score ≥2) were determined. MIBG/99mTc-tetrofosmin mismatch was quantified using regions with preserved innervation as the reference for scaling 99mTc-tetrofosmin voxel maps. Quantification techniques were tested on studies of 619 ischemic (I) and 319 non-ischemic (NI) HF subjects. Using all analytical techniques, IHF subjects had significantly greater and more severe MIBG SPECT abnormalities compared with NIHF subjects. Innervation/perfusion mismatches were also larger in IHF subjects. Findings were consistent between voxel- and myocardial-segment-based quantitation methods. CONCLUSIONS: Multiple objective methods for quantitation of MIBG SPECT imaging studies provided internally consistent results for distinguishing the different patterns of uptake between IHF and NIHF subjects.

Impact of medications on mIBG uptake, with specific attention to the heart: Comprehensive review of the literature.

BACKGROUND: A critical review of the literature on drug interactions with mIBG uptake was performed to allow formulation of contemporary guidance regarding withholding medications prior to clinical imaging studies. METHODS: Published information was extracted on the experimental system used, the quantitative characteristics of the measurements, and whether any data directly examining cardiac tissues were included. Level of evidence for each medication category was assessed on a qualitative scale of very low, low, medium, or high. Strength of medication effect for inhibition of mIBG uptake was judged as none, weak, moderate, or strong. RESULTS: The only medications for which level of evidence was judged high were labetalol and reserpine. Level of evidence was judged medium for tricyclic antidepressants, calcium channel blockers, and antiarrhythmics (specifically amiodarone). Evidence was judged sufficient to recommend withholding labetalol and the tricyclic antidepressants prior to mIBG cardiac imaging. Mechanistic evidence was sufficient to suggest consideration of withdrawal of sympathomimetic amines and serotonin-norepinephrine reuptake inhibitors (SNRIs). CONCLUSIONS: As there is strong evidence for inhibition of mIBG uptake in only a small number of compounds, clinical decisions regarding withdrawal of concomitant medications should be individualized by considering the potential consequences of a false-positive (artificially low cardiac uptake) imaging result.

Incremental utility of iodine-123 meta-iodobenzylguanidine imaging beyond established heart failure risk models.

BACKGROUND: Nuclear myocardial imaging with iodine-123 meta-iodobenzylguanidine ((123)I-mIBG) is approved for risk stratification of patients with systolic heart failure (HF). Whether (123)I-mIBG imaging provides incremental prognostic utility beyond established risk models remains unclear. METHODS AND RESULTS: In a multicenter study, 961 patients with moderate systolic HF underwent (123)I-mIBG imaging and were followed for cardiac death, progressive HF, or life-threatening arrhythmias over 2 years. We constructed 4 multivariable models, using variables from each of 4 published HF risk models, and patient-level scores were calculated both before and after adding the heart-to-mediastinum ratio (H/M) from (123)I-mIBG imaging. Incremental utility was evaluated by calculating integrated discrimination improvement (IDI), which quantifies the increase in probability of experiencing the primary end point after adding H/M to each model. The composite end point occurred in 25% of patients. After adding H/M, absolute IDI ranged from 2.1% to 3.0%, representing 33%-59% relative improvements in risk stratification. Of note, hazard ratios for H/M were remarkably similar between risk models (0.40-0.44 for predicting the composite end point, 0.10-0.18 for mortality; all P < .001). CONCLUSIONS: Despite notable differences in predictor variables, patient populations, and analytic techniques from which each model was initially derived, adding (123)I-mIBG data to HF risk models consistently identified patients at lower risk of experiencing adverse events.

Relationship between quantitative cardiac neuronal imaging with ¹²³I-meta-iodobenzylguanidine and hospitalization in patients with heart failure.

PURPOSE: Hospitalization in patients with systolic heart failure is associated with morbidity, mortality, and cost. Myocardial sympathetic innervation, imaged by (123)I-meta-iodobenzylguanidine ((123)I-mIBG), has been associated with cardiac events in a recent multicenter study. The present analysis explored the relationship between (123)I-mIBG imaging findings and hospitalization. METHODS: Source documents from the ADMIRE-HF trial were reviewed to identify hospitalization events in patients with systolic heart failure following cardiac neuronal imaging using (123)I-mIBG. Time to hospitalization was analyzed with the Kaplan-Meier method and compared to the mIBG heart-to-mediastinum (H/M) ratio using multiple-failure Cox regression. RESULTS: During 1.4 years of median follow-up, 362 end-point hospitalizations occurred in 207 of 961 subjects, 79 % of whom had H/M ratio <1.6. Among subjects hospitalized for any cause, 88 % had H/M ratio <1.6 and subjects with H/M ratio <1.6 experienced hospitalization earlier than subjects with higher H/M ratios (log-rank p = 0.003). After adjusting for elevated brain natriuretic peptide (BNP) and time since heart failure diagnosis, a low mIBG H/M ratio was associated with cardiac-related hospitalization (HR 1.48, 95 % CI 1.05 - 2.0; p = 0.02). CONCLUSION: The mIBG H/M ratio may risk-stratify patients with heart failure for cardiac-related hospitalization, especially when used in conjunction with BNP. Further studies are warranted to examine these relationships.

A prediction model for 5-year cardiac mortality in patients with chronic heart failure using ¹²³I-metaiodobenzylguanidine imaging.

PURPOSE: Prediction of mortality risk is important in the management of chronic heart failure (CHF). The aim of this study was to create a prediction model for 5-year cardiac death including assessment of cardiac sympathetic innervation using data from a multicenter cohort study in Japan. METHODS: The original pooled database consisted of cohort studies from six sites in Japan. A total of 933 CHF patients who underwent (123)I-metaiodobenzylguanidine (MIBG) imaging and whose 5-year outcomes were known were selected from this database. The late MIBG heart-to-mediastinum ratio (HMR) was used for quantification of cardiac uptake. Cox proportional hazard and logistic regression analyses were used to select appropriate variables for predicting 5-year cardiac mortality. The formula for predicting 5-year mortality was created using a logistic regression model. RESULTS: During the 5-year follow-up, 205 patients (22 %) died of a cardiac event including heart failure death, sudden cardiac death and fatal acute myocardial infarction (64 %, 30 % and 6 %, respectively). Multivariate logistic analysis selected four parameters, including New York Heart Association (NYHA) functional class, age, gender and left ventricular ejection fraction, without HMR (model 1) and five parameters with the addition of HMR (model 2). The net reclassification improvement analysis for all subjects was 13.8 % (p < 0.0001) by including HMR and its inclusion was most effective in the downward reclassification of low-risk patients. Nomograms for predicting 5-year cardiac mortality were created from the five-parameter regression model. CONCLUSION: Cardiac MIBG imaging had a significant additive value for predicting cardiac mortality. The prediction formula and nomograms can be used for risk stratifying in patients with CHF.

The utility of ADMIRE-HF risk score in predicting serious arrhythmic events in heart failure patients: incremental prognostic benefit of cardiac 123I-mIBG scintigraphy.

BACKGROUND: A minority of heart failure (HF) patients who undergo implantable cardioverter defibrillator (ICD) implantation for primary prevention of sudden cardiac death (SCD) receive device therapy. Whether the addition of mIBG scintigraphy to conventional markers of arrhythmic risk can provide incremental risk stratification in HF patients has not been investigated. METHODS: We identified 778 patients from the ADMIRE-HF study with LVEF < 35% and class II or III HF symptoms who did not have an ICD at the time of enrollment. Patients were followed up prospectively (median 5 17 months) for occurrence of arrhythmic events (ArE). Heart-to-mediastinum ratio (HMR) was determined as a measure of relative myocardial sympathetic nerve activity at baseline using 123I-mIBG. The primary endpoint was the first occurrence of ArE: a composite of SCD, appropriate ICD therapy, resuscitated cardiac arrest or sustained ventricular tachycardia. Multivariate regression was used to determine independent predictors of ArE and to derive a risk score for ArE prediction. The score was used to group patients according to their risk for ArE. Integrated discrimination improvement (IDI) was used to quantify improvement in risk assessment with addition of HMR. RESULTS: ArE occurred in 54 patients (6.9%). ArE predictors were:HMR < 1.6 (HR 3.5, 95%CI [1.52-8], P 5 .02), LVEF < 25% (HR 2.0, 95% CI [1.28-3.05], P 5 .04) and SBP < 120 (HR 1.2,95%CI [1.03-1.39], P 5 .02). Event rates in the low-, intermediate-, and high risk groups were 2, 10 and 16%, respectively (P 5 .001). The score significantly improved risk prediction(IDI 5 45%, P 0.03). CONCLUSION: 123I-mIBG significantly provides incremental risk stratification for ArE in HF patients.

The relationship of left ventricular mechanical dyssynchrony and cardiac sympathetic denervation to potential sudden cardiac death events in systolic heart failure.

BACKGROUND: Patients with heart failure (HF) are at increased risk for left ventricular (LV) dyssynchrony which is associated with sudden cardiac death (SCD). This study examined the association of LV mechanical dyssynchrony and cardiac sympathetic denervation with potential SCD events in symptomatic patients with HF and reduced ejection fraction (HFrEF). METHODS: Of the 917 HFrEF patients in ADMIRE-HF, 92 experienced adjudicated potential SCD events during a 17 months median follow-up. Propensity scores were used to assemble a matched cohort of 85 pairs of patients with and without potential SCD events. ADMIRE-HF subjects had rest gated SPECT Tc-99m and I-123 MIBG imaging. Perfusion images were processed using phase analysis software to derive phase standard deviation (SD), an index of mechanical dyssynchrony. RESULTS: Of the 92 patients who experienced adjudicated potential SCD events 23 had SCD, 5 fatal myocardial infarction, 7 resuscitated cardiac arrest, 46 had appropriate ICD therapy, and 11 had sustained ventricular tachycardia. Patients who experienced potential SCD events had significantly wider phase SD than matched control patients (62.3 ± 2.4º vs 55.5 ± 2.3º, P = .03) and were more likely to have a phase SD ≥ 60º (53 % vs 35 %, P = .03). Fewer patients with potential SCD events (6 % vs 15 % of the controls, P = .08) had an MIBG heart/mediastinum uptake-ratio ≥1.6. CONCLUSIONS: Among symptomatic HFrEF patients, LV mechanical dyssynchrony is independently associated with potential SCD events. Phase analysis may provide incremental prognostic information on top of current indicators of SCD risk in HFrEF.

I-123 mIBG and Tc-99m myocardial SPECT imaging to predict inducibility of ventricular arrhythmia on electrophysiology testing: a retrospective analysis.

OBJECTIVES: The purpose of this study is to assess mIBG uptake in scar border zone and its relation with ventricular arrhythmia (VA) inducibility on electrophysiology (EP) testing using I-123 mIBG SPECT and resting Tc-99m SPECT myocardial perfusion imaging (MPI). METHODS: Forty-seven patients from a previous clinical trial were retrospectively analyzed. These patients underwent I-123 mIBG and resting Tc-99m tetrofosmin SPECT, and EP testing. Twenty-eight patients were positive (EP+) and 19 patients were negative (EP-) for inducibility of sustained (>30 seconds) VA on EP testing. MPI scar extent, border zone extent, and mIBG uptake in border zone were used to predict VA inducibility on EP testing, respectively. RESULTS: There was no significant difference in scar extent between the EP+ and EP- groups. The EP+ group had significantly larger border zone and lower mIBG uptake ratio in the border zone than the EP- group. Receiver operating characteristic (ROC) curve analysis showed that the prediction accuracy for border zone extent (area under ROC = 0.75) was better than scar extent (area under ROC = 0.66). The prediction accuracy was further improved (area under ROC = 0.78), when assessing mIBG uptake in the border zone. CONCLUSION: A new tool has been developed to measure scar and border zone and to assess mIBG uptake in scar and border zone from combined I-123 MIBG SPECT and resting Tc-99m SPECT MPI. The mIBG uptake in the border zone predicted VA inducibility on EP testing with a promising accuracy.

Influence of myocardial region of interest definition on quantitative analysis of planar 123I-mIBG images.

PURPOSE: In planar (123)I-mIBG myocardial imaging, definition of the heart region of interest (ROI) is a critical step in quantifying uptake. The present study evaluated the impact of changes in heart ROI size on quantitative results in subjects with good and poor uptake. METHODS: Reference irregular whole-heart and square upper mediastinum ROIs were defined visually on 531 planar (123)I-mIBG images. Based on the reference heart ROI, an automated program created two other ROIs: one larger (+1 pixel) and one smaller (-1 pixel), the stated numbers representing the spacing intervals between each epicardial boundary pixel. Two additional smaller ROIs (-2 and -3 pixels) were drawn for the 100 images (19 %) with a heart/mediastinum (H/M) ratio ≤1.30. The number of pixels, the counts per pixel, and the H/M ratio for each heart ROI were calculated and compared to that in the reference ROI. Washout rate and changes as a function of ROI size were also calculated for 110 subjects who had both early and late images. RESULTS: The mean changes in heart ROI size ranged from +19.0 % for the +1 pixel to -44.4 % for the -3 pixels ROI. For the +1 and -1 pixel ROIs, mean relative counts per pixel changes were -1.2 % and +0.7 %, respectively, with corresponding ranges of change in the H/M ratio of -0.12 to +0.05 and -0.05 to +0.11. For scans with H/M ratio ≤1.30, mean relative counts per pixel changes were 0, 0, -0.7 %, and -1.4 % for the four ROIs, with range of change in the H/M ratio from -0.13 to +0.05. Mean washout rates were almost identical for the reference ROIs (45.0 %) and the +1 pixel and -1 pixel heart ROIs (44.9 % and 45.1 %, respectively). CONCLUSION: Significant changes in the size of the best visually defined heart ROI produce minimal, clinically inconsequential changes in the H/M ratio and washout rate, even in subjects with significantly reduced myocardial uptake of (123)I-mIBG.

Outcome prediction in heart failure with atrial fibrillation: relative role of left ventricular ejection fraction and neurohormonal measures.

BACKGROUND: Since atrial fibrillation (AF) impacts the measurement and interpretation of left ventricular ejection fraction (LVEF), we hypothesized that the outcome in heart failure (HF) with AF and LVEF ≤ 35% would be more strongly associated with neurohormonal measures than LVEF. METHODS AND RESULTS: Cardiac adverse events [CAE; HF progression (HFP), life-threatening arrhythmia (ARR), and cardiac death (CD)] and all-cause mortality (ACM) were recorded prospectively in 954 patients with HF and LVEF ≤ 35%: 852 in sinus rhythm (SR) and 102 in AF. Cox proportional hazard models found that the univariate hazard ratios (HR) for LVEF and the first CAE (primary outcome), HFP, ARR, CD, and ACM were significant in SR (0.933, P < .001, 0.933, P < .001, 0.929, P < .001, 0.916, P < .001, 0.945, P = .001, respectively), but not in AF (1.002, P = .95, 1.060, P = .24, 0.922, P = .15, 0.885, P = .09, 0.932, P = .25). HRs for CAEs and ACM and one or more neurohormonal measures (iodine 123 m-iodobenzylguanidine cardiac parameters, B-type natriuretic peptide, and plasma norepinephrine) were significant in SR and AF. The multivariate models for the first CAE and HFP included neurohormonal measures and LVEF in SR and neurohormonal measures in AF. CONCLUSIONS: In HF with LVEF ≤ 35% with AF, neurohormonal measures, but not LVEF, were related to outcomes.

Impact of age on myocardial uptake of ¹²³I-mIBG in older adult subjects without coronary heart disease.

BACKGROUND: The purpose of this study was to examine the relationship between myocardial uptake of (123)I-mIBG and age in older normal adult subjects. METHODS: 94 subjects (age 29-82, mean 58.5) without coronary heart disease were studied. All subjects underwent early and delayed planar and 4-hour SPECT (123)I-mIBG imaging. (123)I-mIBG uptake was quantified as heart/mediastinum ratio on planar images (H/M p) and on SPECT images (H/M s) reconstructed by filtered backprojection, ordered subsets-expectation maximization (OSEM), and OSEM with compensation for collimator septal penetration (DSP). Relationships between age and (123)I-mIBG uptake were examined by correlation analysis, t-tests, and analysis of variance. RESULTS: There was no significant correlation between age and H/M p, reflecting comparable increases in activity in the two regions of interest with age. Results on SPECT analyses were comparable, with no significant correlation between age and H/M s. Using DSP, (123)I-mIBG H/M s was significantly higher in subjects ≥70 of age compared with younger subjects. CONCLUSIONS: Both cardiac and background uptake of (123)I-mIBG increase with age in older subjects without coronary heart disease, resulting in stability of H/M results (planar and SPECT). This study suggests that prognostic analyses of quantitative (123)I-mIBG uptake in patients with heart disease do not require adjustment for patient age.

Significance of I-123 metaiodobenzylguanidine (¹²³I-MIBG) lung activity in subjects with heart failure in comparison to healthy control subjects.

BACKGROUND: Little is known concerning the significance of lung activity of the sympathetic neuronal imaging agent (123)I-MIBG in heart failure patients and healthy subjects. METHODS: (123)I-MIBG activity was assessed in lung, heart, and mediastinum regions of interest on early and late planar images in 951 heart failure patients and 94 controls. Cox regression analyses were performed to identify factors associated with outcome events during a median 17 month follow-up. RESULTS: Heart failure subjects with pulmonary disease had significantly reduced late lung-to-mediastinum (L/M) ratios compared to heart failure subjects without pulmonary disease. Late L/M ratio was greater in heart failure subjects without outcome events than either subjects with events or healthy controls. L/M ratio was an independent predictor of all-cause mortality. Subjects with combined favorable prognosis L/M ratio ≥ 1.7 and heart-to-mediastinum ratio (H/M) ≥ 1.6 had a significantly lower 2-year mortality (2.0%) than subjects with unfavorable L/M ratio < 1.7 and H/M ratio < 1.6 (17.7% 2-year mortality, P < .0008). CONCLUSIONS: Increased (123)I-MIBG lung activity in heart failure subjects, compared to controls, is associated with a relatively low risk of adverse events, including all-cause mortality. L/M ratio may, therefore, be useful to provide incremental prognostic information on (123)I-MIBG imaging.

Resting perfusion MPI-SPECT combined with cardiac 123I-mIBG sympathetic innervation imaging improves prediction of arrhythmic events in non-ischemic cardiomyopathy patients: sub-study from the ADMIRE-HF trial.

BACKGROUND: Delayed Iodine-123 meta-iodobenzylguanidine heart/mediastinum (H/M) uptake ratio predicted arrhythmic events in patients with heart failure (HF) and significant left ventricular dysfunction in ADMIRE-HF. We tested the hypothesis that resting perfusion defects on MPI-SPECT, representing scar, would further risk stratify patients beyond H/M ratio in the prediction of ventricular arrhythmic events in both ischemic (ICM) and non-ischemic cardiomyopathy (NICM) patients. METHODS: Patients from the ADMIRE-HF database were classified as ICM and NICM and were stratified by delayed H/M ratio (<1.6/≥1.6) and by summed rest score (SRS) (≤8/>8) on MPI-SPECT. The entire cohort was also classified as high risk (H/M <1.6, SRS >8) and low risk (H/M ≥1.6, SRS ≤8). Scores were from visual interpretation of individual and derived consensus (average) reads per ASNC guidelines. RESULTS: There were 612 (66%) ICM and 317 (34%) NICM patients. ICM patients had higher mean SRS than NICM patients (25 ± 13 vs 12 ± 10). Sixty-three arrhythmic events occurred over a median follow-up of 17 months. SRS had incremental predictive value among NICM patients with low H/M ratio (<1.6). There was no risk stratification in patients with ICM. Multivariable analysis for NICM with H/M ratio <1.6 demonstrated SRS score >8 as the only independent predictor of arrhythmic events (hazard ratio 3.3, 95% CI 1.1-9.8, P = .03). Patients classified in high-risk subgroup had statistically significant increased risk of arrhythmic events (hazard ratio 2.080, 95% CI 1.112-3.894, P = .022). There was only one event in low-risk subgroup with a trend towards lower risk of arrhythmic events (P = .07). CONCLUSION: Resting perfusion defects provide independent risk stratification in addition to Iodine-123 meta-iodobenzylguanidine sympathetic innervation imaging in predicting arrhythmic events in patients with NICM and HF. High and potentially low-risk groups for arrhythmic events can be identified based on the severity of resting perfusion defect score and H/M ratio.

Quantitative I-123 mIBG SPECT in differentiating abnormal and normal mIBG myocardial uptake.

BACKGROUND: The purpose of this study was to evaluate global quantitation of cardiac uptake on I-123 mIBG SPECT. METHODS: The study included a pilot group of 67 subjects and a validation group of 1,051 subjects. SPECT images were reconstructed by filtered backprojection, ordered subsets expectation maximization, and deconvolution of septal penetration, respectively. SPECT heart-to-mediastinum ratio (H/M) was calculated by comparing the mean counts between heart and mediastinum volumes of interest drawn on transaxial images. Receiver operating characteristic (ROC) analysis was used to assess the capability of each SPECT method to differentiate the heart disease subjects from controls in comparison with that of the planar H/M. RESULTS: In the validation group, the areas under the ROC curves were not significantly different between the SPECT and planar H/M. Order subsets expectation maximization had significantly larger area under the ROC curve than the other two SPECT methods. CONCLUSION: H/M obtained from I-123 mIBG SPECT was equivalent to the planar H/M for differentiating between subjects with normal and abnormal mIBG uptake. Global quantification of cardiac I-123 mIBG SPECT may represent a viable alternative to the planar H/M.

Selective improvement in Seattle Heart Failure Model risk stratification using iodine-123 meta-iodobenzylguanidine imaging.

BACKGROUND: The Seattle Heart Failure Model (SHFM) is a multivariable model that uses demographic and clinical markers to predict survival in patients with heart failure. Inappropriate activation of the sympathetic nervous system, which contributes to the progression of heart failure and increased mortality, can be assessed using iodine-123 meta-iodobenzylguanidine (MIBG) cardiac imaging. This study investigated the incremental value of MIBG cardiac imaging when added to the SHFM for prediction of all-cause mortality. METHODS: Survival data from 961 NYHA II-III subjects in the ADMIRE-HFX trial were included in this analysis. The predictive value of the SHFM alone and in combination with MIBG heart-to-mediastinum ratio (H/M) was compared for all-cause mortality (101 deaths during a median follow-up of 2 years). RESULTS: The addition of H/M to the SHFM in a Cox model significantly improved risk prediction (P < .0001), with a greater utility in higher risk SHFM patients. The observed 2-year mortality in the highest-risk SHFM subjects (rounded SHFM score of 1) was 24%, but varied from 46% with H/M <1.2 to 0% with H/M >1.8. Net reclassification improvement was 22.7% (P < .001), with 14.9% of subjects who died reclassified into a higher risk category than suggested by SHFM score alone (P = .01) and 7.9% of subjects who survived reclassified into a lower risk category (P < .0001). The 2-year integrated discrimination improvement (+4.14%, P < .0001) and the 1-year area under the receiver-operator characteristic curve (+0.04, P = .026) both showed significant improvement for the combined model with H/M compared to the SHFM alone. CONCLUSION: The addition of MIBG imaging to the SHFM improves risk stratification, especially in higher risk patients. MIBG may have clinical utility in higher risk patients who are being considered for devices such as ICD, CRT-D, LVAD, and cardiac transplantation.

A simplified wall-based model for regional innervation/perfusion mismatch assessed by cardiac 123I-mIBG and rest 99mTc-tetrofosmin SPECT to predict arrhythmic events in ischaemic heart failure.

AIMS: Cardiac 123iodine-meta-iodobenzylguanidine (123I-mIBG) single-photon emission computed tomography (SPECT) imaging provides information on regional myocardial innervation. However, the value of the commonly used 17-segment summed defect score (SDS) as a prognostic marker is uncertain. The present study examined whether a simpler regional scoring approach for evaluation of 123I-mIBG SPECT combined with rest 99mTc-tetrofosmin SPECT myocardial perfusion imaging could improve prediction of arrhythmic events (AEs) in patients with ischaemic heart failure (HF). METHODS AND RESULTS: Five hundred and two ischaemic HF subjects of the ADMIRE-HF study with complete cardiac 123I-mIBG and rest 99mTc-tetrofosmin SPECT studies were included. Both SPECT image sets were read together by two experienced nuclear imagers and scored by consensus. In addition to standard 17-segment scoring, the readers classified walls (i.e. anterior, lateral, inferior, septum and apex) as normal, matched defect, mismatched (innervation defect > perfusion defect), or reverse mismatched (perfusion defect > innervation defect). Cox proportional hazards ratios (HRs) were used to determine if age, body mass index, functional class, left ventricular ejection fraction (LVEF), B-type natriuretic peptide (BNP), norepinephrine, 123I-mIBG SDS, 99mTc-tetrofosmin SDS, innervation/perfusion mismatch SDS, and our simplified visual innervation/perfusion wall classification were associated with occurrence of AEs (i.e. sudden cardiac death, sustained ventricular tachycardia, resuscitated cardiac arrest, appropriate implantable cardioverter-defibrillator therapy). At 2-year median follow-up, 52 subjects (10.4%) had AEs. Subjects with 1 or 2 mismatched walls were twice as likely to have AEs compared with subjects with either 0 or 3-5 mismatched walls (16.3% vs. 8.3%, P = 0.010). Cox regression analyses showed that patients with a visual mismatch in 1-2 walls had an almost two times higher risk of AEs [HR 2.084 (1.109-3.914), P = 0.001]. None of the other innervation, perfusion and mismatch scores using standard 17 segments were associated with AEs. BNP (ng/L) was the only non-imaging parameter associated with AEs. CONCLUSION: A visual left ventricular wall-level based scoring method identified highest AE risk in ischaemic HF subjects with intermediate levels of innervation/perfusion mismatches. This simple technique for the evaluation of SPECT studies, which are often challenging in HF subjects, seems to be superior to the 17-segment scoring method.